Dr. Marianne Anderson is an Assistant Professor of Pediatrics and a board-certified Neonatologist at The University of Colorado School of Medicine. She has considerable experience in whole animal studies of glucose uptake and transport in the fetal sheep skeletal muscle. Her immediate goals are to learn sophisticated tracer methods to study substrate interactions and metabolism in vivo and to learn techniques of molecular and cell biology to study the mechanisms and regulation of those interactions in vitro. Her long term goal is to develop an independent research career using both in vivo models and in vitro techniques to investigate how fetal adaptations to nutritional changes impact growth, metabolism, and, ultimately, adult well being. The University of Colorado Perinatal Research Center, with a well established large animal sheep facility and a recently completed Molecular Biology Core Laboratory, provides an ideal environment for Dr. Anderson to achieve her immediate and long term goals. She will be mentored by Wlliam W. Hay, Jr., M.D. and Jacob E. Friedman, Ph.D., both of whom have extensive experience and stature in their respective fields of glucose metabolism and insulin signaling. Dr. Hay, her primary mentor, will continue to support her learning surgical techniques and physiologic study designs and methods, including radioactive and stable isotope tracer methodology. Dr. Friedman will provide expertise in insulin signaling and training in molecular concepts and techniques. Dr. Anderson's previous research has shown that acute variations in glucose or insulin concentration in fetal sheep have independent effects on whole fetal glucose utilization and on glucose transporter protein concentration in several tissues. The overall hypothesis in the current proposal is that chronic changes in fetal glucose supply regulate mechanisms responsible for fetal growth. Clamp technique and tracer methodology will be utilized to produce fetal sheep models of chronic hypo- or hyper-glycemia and measure metabolism in vivo. The effects of the changes in fetal glucose concentrations on the expression of membrane glucose transporters, cellular glucose uptake, insulin sensitivity (via signal transduction and glucose transporter translocation to active membrane sites), and insulin signal transduction and incorporation of amino acids into protein synthesis and cell growth will be studied using molecular techniques.